title: Dioxin-induced acute cardiac mitochondrial oxidative damage and increased activity of ATP-sensitive potassium channels in Wistar rats.
abstract: The environmental dioxin 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is classified as a Group 1 human carcinogen and teratogenic agent. We hypothesize that TCDD-induced oxidative stress may also interfere with mitochondrial ATP-sensitive potassium channels (mitoKATP), which are known to regulate and to be regulated by mitochondrial redox state. We investigated the effects of an acute treatment of male Wistar rats with TCDD (50 μg/kg i.p.) and measured the regulation of cardiac mitoKATP. While the function of cardiac mitochondria was slightly depressed, mitoKATP activity was 52% higher in animals treated with TCDD. The same effects were not observed in liver mitochondria isolated from the same animals. Our data also shows that regulation of mitochondrial ROS production by mitoKATP activity is different in both groups. To our knowledge, this is the first report to show that TCDD increases mitoKATP activity in the heart, which may counteract the increased oxidative stress caused by the dioxin during acute exposure.
authors.affiliation: CNC - Center for Neuroscience and Cell Biology, University of Coimbra, Largo Marquês de Pombal, 3004-517 Coimbra, Portugal. rothenberg.sarah@sc.edu
authors.forename: Susana P
authors.initials: SP
authors.lastname: Pereira
authors.forename: Gonçalo C
authors.initials: GC
authors.lastname: Pereira
authors.forename: Cláudia V
authors.initials: CV
authors.lastname: Pereira
authors.forename: Filipa S
authors.initials: FS
authors.lastname: Carvalho
authors.forename: Marília H
authors.initials: MH
authors.lastname: Cordeiro
authors.forename: Paula C
authors.initials: PC
authors.lastname: Mota
authors.forename: João
authors.initials: J
authors.lastname: Ramalho-Santos
authors.forename: António J
authors.initials: AJ
authors.lastname: Moreno
authors.forename: Paulo J
authors.initials: PJ
authors.lastname: Oliveira
mesh_terms: D000818:Animals; D002273:Carcinogens / Q000633:toxicity*; D004147:Dioxins / Q000633:toxicity*; D054086:KATP Channels / Q000378:metabolism*; D008297:Male; D008930:Mitochondria, Liver / Q000187:drug effects* / Q000378:metabolism; D018384:Oxidative Stress; D015221:Potassium Channels / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D002273:Carcinogens; D004147:Dioxins; D054086:KATP Channels; D015221:Potassium Channels; C117780:mitochondrial K(ATP) channel
keywords: 2,3,7,8-Tetrachlorodibenzo-p-dioxin; 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid; 5-HD; 5-hydroxydecanoic acid; ADP; ATP; AhR; BSA; Bioenergetics; DMSO; DNA; DNPH; DZX; Diazoxide; Dioxin; HEPES; HRP; HW/BW; LW/BW; Mitochondria; PCDD/Fs; RCR; ROS; SDS; TCDD; TFA; TPP(+); adenosine diphosphate; adenosine triphosphate; aromatic hydrocarbon receptor; bovine serum albumin; deoxyribonucleic acid; dimethylsulphoxide; dinitrophenylhydrazine; heart weight/body weight; horseradish peroxidase type vi-a; liver weight/body weight; mitoKATP; mitochondrial ATP-sensitive potassium channels; mitochondrial transmembrane electric potential; polychlorinated dibenzofuran; reactive oxygen species; respiratory control ratio; sodium dodecyl sulfate; tetraphenylphosphonium cation; trifluoroacetic acid; ΔΨ